Cross talk between alpha(v)beta3 and alpha4beta1 integrins regulates lymphocyte migration on vascular cell adhesion molecule 1.
Local inflammation leads to increased expression of the vascular cell adhesion molecule (VCAM)-1 on vascular endothelium which contributes to the encapture of leukocytes from the circulating blood through the leukocyte ligand alpha4beta1 integrin. Inflammatory vascular endothelium expresses VCAM-1 at high density. We found that the speed of locomotion of activated lymphocytes migrating along surfaces coated with recombinant VCAM-1 at a comparable density to that found on inflammatory endothelium was slow. However, lymphocytes do migrate and extravasate rapidly under inflammatory conditions, indicating that there must be mechanisms that regulate the interaction between alpha4beta1 and VCAM-1 in vivo. Here we show that the lymphocyte alpha(v)beta3 integrin and integrin-associated protein (IAP) is able to regulate this interaction. The occupancy of lymphocyte alpha(v)beta3 integrin by platelet cell adhesion molecule-1 or vitronectin regulated the speed of alpha4beta1 integrin-dependent locomotion of lymphocytes on recombinant VCAM-1. This allowed rapid lymphocyte migration at VCAM-1 densities which are typical of inflammatory vessels. This alpha(v)beta3-mediated enhanced migration of lymphocytes via alpha4beta1 is likely to depend on the interaction of alpha(v)beta3 integrin with the IAP. Furthermore, this motile process correlates with polarization of the actin cytoskeleton in lymphocytes. Our results suggest that cross talk between alpha(v)beta3 integrin and alpha4beta1 integrin is a mechanism in the regulation of lymphocyte locomotion along inflammatory endothelium and subsequent transendothelial migration. This can explain how lymphocytes overcome tight adhesion to the vascular endothelium and start rapid migration along and through the endothelial lining of blood vessels into inflammatory tissue.
Imhof
B A
BA
Basel Institute for Immunology, Switzerland. Beat.Imhof@medecine.unige.ch
Weerasinghe
D
D
Brown
E J
EJ
Lindberg
F P
FP
Hammel
P
P
Piali
L
L
Dessing
M
M
Gisler
R
R
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology* / Q000502:physiology; D051379:Mice; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019030:Receptors, Vitronectin; D019010:Vascular Cell Adhesion Molecule-1